The systems controlling the number, size, hemoglobin concentrations, and other characteristics of circulating human red blood cells (RBCs) are poorly understood. After release from the bone marrow, RBCs undergo reduction in both volume and total hemoglobin content by an unknown mechanism (Lew V L, et al. (1995) Blood 86:334-341; Waugh R E, et al. (1992) Blood 79:1351-1358); after about 120 days, responding to an unknown trigger, they are removed.